Sunday, February 16, 2014
migration speed and cytoskeleton organization. Furthermore, cellular migration is monitored on polymer-tethered bilayer substrates with a sharp boundary or lateral gradient in lipopolymer concentration.
874-Pos Board B629
Modeling Follicle Cell Length Oscillations During Tissue Elongation in
Drosophila Egg Chamber
Sarita Koride1, Li He2, Ganhui Lan3, Denise Montell4, Sean Sun1.
1
Johns Hopkins University, Baltimore, MD, USA, 2Harvard Medical School,
Boston, MA, USA, 3George Washington University, Washington, DC, USA,
4
University of California, Santa Barbara, Santa Barbara, CA, USA.
Periodic processes are an indispensable part of biological phenomena. Circadian rhythms, heart rhythms, neuronal oscillations, cell cycle, and cytoskeletal structures such as the axonemes of cilia are all examples of systems
exhibiting oscillatory dynamics. The underlying mechanisms of several
such processes can be explained by understanding the origins of these oscillations and characterizing them. One particular example is the follicle cell
basal surface area oscillations observed in Drosophila egg chamber during
oogenesis. It has been suggested that these oscillations restrict the egg chamber width, and thus help in elongation of the tissue. In this work, we attempt
to model these oscillations in follicle cell length using a mechano-chemical
model. Our model predicts an increase in oscillation period, upon removal of
the basement membrane, which has been observed experimentally upon
collagenase treatment of the egg chamber. The model also predicts an inverse relationship of maximum contractile force and oscillation period.
875-Pos Board B630
Coupling up: How Interactions between Cell Stresses and Intracellular
Biochemistry Affect Cell Spreading
Magdalena Stolarska1, Aravind Rammohan2, Srikanth Raghavan2.
1
University of St. Thomas, St. Paul, MN, USA, 2Corning, Inc., Corning, NY,
USA.
We present a two-dimensional mathematical model and finite element simulations that allow us to better understand how local cellular deformations must be
coupled to the evolution of an intracellular plaque protein that controls the formation of focal adhesions. Specifically, we explore effects of alternate formulations for coupling cellular response to substrate mechanics. Further, we also
investigate the effect of initial cellular shape on cell spreading and intracellular
stresses. Our aim is to determine whether the initial anisotropy of a cell predisposes it to remain anisotropic during spreading. In addition, we examine the
role of focal adhesion strength in maintaining anisotropy. In the models for
cell and substrate mechanics we assume that the cell is an active hypoelastic
material and the substrate is linearly elastic. Focal adhesions are modeled as
a collection of discrete springs that can be added and removed dynamically.
This work aims to unearth some of the fundamental mechanisms in cell-substrate interactions.
876-Pos Board B631
Calculating Intercellular Stress in a Model of Collectively Moving Cells
Juliane Zimmermann1, Markus Basan2, Ryan Hayes1, Wouter-Jan Rappel2,
Eshel Ben-Jacob1, Herbert Levine1.
1
Center for Theoretical Biological Physics, Rice University, Houston, TX,
USA, 2Center for Theoretical Biological Physics, University of California at
San Diego, La Jolla, CA, USA.
Cells move together in groups during development, wound healing, and cancer metastasis. It remains unclear how collectively moving cells coordinate
their motion. In addition to external chemoattractants and exchanging
signaling molecules, cells may also respond to mechanical cues. We developed a model of collective cell migration under the assumption that cells
align their motility force with the direction of their velocity. This simple
mechanism leads to large scale velocity correlations, swirling motion in
the bulk of monolayers, and finger-like protrusions at the edge [1]. In experimental studies, the inter- and intracellular stress in the monolayer has been
calculated from measured traction forces between the cells and the substrate.
Stress builds up successively towards the center of the tissue as the majority
of the cells pull outwards [2]. While one dimensional stress profiles are
based on a simple force balance, two dimensional stress maps require the
additional assumption of an elastic tissue [3], and the validity of this
assumption remains disputable. In our model simulations, both the forces
on the substrate and the intercellular forces are accessible. We can therefore
apply a second method to calculate the stress based on forces between cells.
Stress patterns calculated with both methods agree, showing that recovery of
the intercellular stress is indeed mostly independent of specific material
properties.
173a
1. Basan, M., J. Elgeti, E. Hannezo, W.-J. Rappel and H. Levine. PNAS. 2013.
2. Trepat, X., M. R. Wasserman, T. E. Angelini, E. Millet, D. A. Weitz, J. P.
Butler and J. J. Fredberg. Nat. Phys. 2009.
3. Tambe, D. T., C. Corey Hardin, T. E. Angelini, K. Rajendran, C. Y. Park, X.
Serra-Picamal, E. H. Zhou, M. H. Zaman, J. P. Butler, D. A. Weitz, J. J. Fredberg and X. Trepat. Nat. Mater. 2011.
877-Pos Board B632
Combination of Chemotaxis and Differential Adhesion Leads to Robust
Cell Sorting During Tissue Patterning
Rui Zhen Tan1, Keng-Hwee Chiam2,1.
1
Bioinformatics Institute, Singapore, Singapore, 2National University of
Singapore, Singapore, Singapore.
Robust tissue patterning is crucial to many processes during development.
The ‘‘French Flag’’ model of patterning by instructive morphogen concentrations has been the most widely proposed model for tissue patterning. However, recently, cell sorting has been found to be an alternative model. In
this article, we used computational modeling to show that two mechanisms,
namely chemotaxis and differential adhesion, are needed for robust cell sorting. We assessed the performance of each of the two mechanisms by quantifying the fraction of correct sorting, the fraction of stable clusters after
correct sorting, time taken for correct sorting and the size variations of the
cells having different fates. We found that chemotaxis and differential adhesion confer different advantages to the sorting process. Chemotaxis leads to
high fraction of correct sorting whereas differential adhesion leads to high
fraction of stable clusters. A combination of both chemotaxis and differential
adhesion yields cell sorting that is both accurate and robust. Thus, we propose
that both mechanisms are used for cell sorting during tissue patterning in
development.
878-Pos Board B633
Catching up on Slip: Focal Adhesion Composition and Mechanosensing
Elizaveta A. Novikova1,2, Cornelis Storm1,2.
1
Applied Physics, Eindhoven University of Technology, Eindhoven,
Netherlands, 2Institute for Complex Molecular Systems, Eindhoven,
Netherlands.
Unlike slip bonds, catch bonds experience reinforcement under tension. Cell
adheres to the surface, using integrins forming both catch- and slip- bonds
with the surface receptors. How will the catch and slip bonds interact with
each other on a single adhesion scale? How does the intracellular structure
vary depending on the extracellular matrix stiffness? I discuss the implications of single catch-bond characteristics for the behavior of a load-sharing
cluster of such bonds: these are shown to possess a regime of strengthening
with increasing applied force, similar to the manner in which focal adhesions
become selectively reinforced. In addition, I present numerical simulations of
mixtures of catch and slip bonds within single focal adhesion, and propose a
model of how they can influence cytoskeletal reorganization, force generation and adhesion growth, interacting indirectly through applied force. Our
results may shed new light on the fundamental processes that allow cells
to sense the mechanical properties of their environment and in particular
show how single focal adhesions may act, autonomously, as local rigidity
sensors.
879-Pos Board B634
Influence of Substrate Stiffness and Thickness on Cell Traction Forces
Aravind R. Rammohan, Srikanth Raghavan.
Corning Inc., Corning, NY, USA.
It is known that various cell types can sense and respond to the mechanical
properties of their microenvironment. Specifically, cells have been known to
spread more when cultured on stiff substrates [1-3] and are able to match
their internal stiffness to that of the substrate [2, 3]. Recent works have reported on dynamics of cellular properties such as cell shape, cell spread
area, and focal adhesion area, as functions of environmental properties
such as substrate stiffness, thickness, and chemistry. Building on earlier
models [4, 5, 6], we present mathematical models that enable us to replicate
some aspects of experimentally reported time-dependent cell behavior. Our
models investigate the adaptation of internal cell stiffness through increase
in number of focal adhesion complexes and temporal build-up of traction
force. Our models crucially invoke the ability of some cell types to adapt
their internal stiffness and show that substrate stiffness and thickness can
strongly assist in rapid build-up of traction forces and formation of multiple
cooperative focal adhesion complexes. Further using our models we generate
some mechanistic insights into why certain cell types under the influence of
specific substrate properties exhibit the kind of dynamics that has been